A Study to Develop Predictive and Prognostic Tools for Optimizing Therapy With Bevacizumab Frontline Cancer Therapy in Participants With HER 2-Negative Aggressive Metastatic Breast Cancer

Breast Cancer Clinical Trial

— Argo  

Official title:

Observational and Prospective Study to Develop Predictive and Prognostic Tools for Optimizing Therapy With Bevacizumab Frontline Cancer Therapy in Patients With Metastatic HER 2-Negative and Aggressive Disease Criteria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02613208
• Other study ID #: ML29756
• Secondary ID: ROC-BEV-2015-01
• Status: Completed
• Start date: December 9, 2015
• Est. completion date: December 3, 2018

Study information

• Verified date: February 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This multicenter, observational, prospective study will identify a powerful and easy predictive/prognostic marker to use with participants under bevacizumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: December 3, 2018
• Est. primary completion date: December 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants with HER2-negative metastatic breast cancer. Mandatory to have the HER2/estrogen receptor (ER)/progesterone receptor (PR) status

• Participant who met criteria for first-line treatment with chemotherapy plus bevacizumab (standard doses) by local, regional or national guidelines or authorities

• Participants with measurable disease (RECIST criteria v1.1) or participants with no measurable but assessable disease

• Molecular phenotype as triple negative metastatic breast cancer; and ER-positive tumors need to fulfill at least one of the two clinical criteria: metastatic relapse on adjuvant endocrine therapy or progression to at least one prior line of endocrine therapy for advanced disease; or aggressive disease criteria (at least two criteria): taxane based regimen in the (neo) adjuvant setting; metastatic relapse within 2 years from the end of chemotherapy for early breast cancer; liver metastasis; three or more organs with metastatic involvement; symptomatic visceral disease

• Eastern Cooperative Oncology Group (ECOG) 0-2

Exclusion Criteria:

• Participant has received prior chemotherapy for metastatic disease

• Participant requiring major/minor surgery within 3 weeks prior to administration of the first dose of study treatment

• Participant has received an investigational therapy within 4 weeks prior to study entry

• Participant has known symptomatic brain metastases

• Participant with non-measurable or assessable disease: exclusive blastic bone disease; pleural, pericardial or abdominal effusion as only evidence of disease

• Participant in chronic daily treatment with corticosteroids (doses greater than [>]10 milligrams per day [mg/day] of methylprednisolone or equivalent), except inhaled steroids

• Pregnant or breastfeeding participant

• Women of childbearing potential who are not using hormonal contraceptives or highly effective birth control during the study

• Participant has an active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy

• Participant with significant renal, hematological or liver function alteration according to investigator's criteria

• Participant has serious medical risk factors involving any of the major organ systems

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab will be administered as per local clinical practice and local labeling.
• Paclitaxel
Paclitaxel will be administered as per local clinical practice and local labeling.

Locations

Country	Name	City	State
Spain	Hospital Quiron Barcelona; Servicio de Oncologia	Barcelona
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital Universitario Virgen de las Nieves; Servicio de Oncologia	Granada
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	La Coruna	LA Coruña
Spain	Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia	Las Palmas de Gran Canaria	LAS Palmas
Spain	Complejo Asistencial Universitario de Leon; Servicio de Oncologia	Leon
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida
Spain	Hospital Lucus Augusti; Servicio de Oncologia	Lugo
Spain	Centro Oncologico MD Anderson Internacional; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario de la Princesa; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia	Murcia
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia	Murcia
Spain	Hospital de Navarra; Servicio de Oncologia	Navarra
Spain	Hospital Universitario Son Espases; Servicio de Oncologia	Palma De Mallorca	Islas Baleares
Spain	Hospital Clinico Universitario de Salamanca; Servicio de Oncologia	Salamanca
Spain	Hospital de Donostia.; Servicio de Oncología Radioterápica	San Sebastián	Guipuzcoa
Spain	Hospital General de Segovia; Servicio de Oncologia	Segovia
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
Spain	Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia	Valencia
Spain	Hospital Universitario Dr. Peset; Servicio de Oncologia	Valencia
Spain	Complejo Hospitalario Zamora- H. Virgen de la Concha; Servicio Oncologia	Zamora

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Clinical Benefit	Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. Results for clinical benefit were reported for 2 groups based on Circulating Tumor Cells (CTC) Levels. The Sensitive group had CTC levels <5 (<5 CTCs in one of the two determinations) and Resistant group had CTC =5 (= 5 CTCs in the two determinations).	During follow-up (up to 18 months)
Secondary	Percentage of Participants With Overall Response as Assessed Using RECIST v1.1	Overall response = Complete Response (CR) + Partial Response (PR). Overall response was evaluated for the Sensitive group (CTC <5) and Resistant group (CTC =5).	From Baseline up to end of study (up to 18 months)
Secondary	Progression Free Survival (PFS) as Assessed Using RECIST v1.1	PFS was evaluated for the Sensitive group (CTC <5) and Resistant group (CTC =5).	From Baseline up to end of study (up to 18 months)
Secondary	Overall Survival	OS was evaluated for the Sensitive group (CTC <5) and Resistant group (CTC =5).	From Baseline up to end of study (up to 18 months)
Secondary	Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4	Adverse events (AEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0). Any AEs that are not specifically listed in the NCI CTCAE follow the logic - Grade 3) Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4: Life-threatening consequences or urgent intervention indicated.	From Baseline up to end of study (up to 18 months)
Secondary	Optimal Cut-off for Clinical Benefit	Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. The optimal cut-off for clinical benefit was calculated from a Receiver Operating Curve (ROC) based on CTC level and used to define the prognostic factors that could better predict clinical outcomes.	Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days)
Secondary	Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups	Overall response = CR + PR. An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups.	Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days)
Secondary	PFS as Assessed Using RECIST v1. in Prognostic Groups	An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups.	From Baseline up to end of study (up to 18 months)
Secondary	Mean CTC Count Levels	CTC and CEA levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered.	Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Secondary	Mean Carcinoembryonic Antigen (CEA) Levels		Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Secondary	Mean Biomarker Cancer Antigen 15.3 (CA 15.3) Level	CTC and CA 15.3 levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered.	Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])